SMAD4 and colonic neoplasm: Using ACVR2A/TGFBR2 wild type FET colon cancer cells, FET with SMAD4 knockdown, and the SMAD4-null colon cancer cell line SW480, we found a SMAD4-independent increase in pAkt Ser473 after activin treatment compared to control and TGFβ treatment (Fig. 2a).